Since thrombotic occlusion of coronary artery saphenous vein bypass graft occurs in the first two weeks and negates the benefits of aortocoronary bypass surgery in about 25% of the patients with coronary artery disease, we have conducted experiments in dogs to elucidate the mechanisms of graft occlusion as well as experiments to determine the potential beneficial effects of the combination of platelet antiaggregating agents. Tracer and electron microscopic studies conducted during the last eight months of this grant have indicated that administration of platelet antiaggregating drugs decreases the incidence of early thrombosis and late intimal proliferation. These studies also suggest that the thrombotic graft occlusion in the early phase is initiated by endothelial damage during harvesting of the vein graft. With the use of labeled platelets, we have developed quantitative technique of evaluation of thrombus formation on vein graft. The most significant achievement during the past year was the direct proof that the oral administration of platelet antiaggregating agents significantly (P less than 0.05) decreased the incidence of early thrombus formation in the coronary artery saphenous vein bypass graft. This findings is of critical importance since it indicates that (a) de-endothelialization of the vein wall occurs during harvesting and implantation of the graft and predisposes to intraluminal thrombosis and (b) that results of coronary artery bypass surgery in patients with coronary artery disease may be improved with the use of anti-platelet drugs by reducing the incidence of early graft occlusion. The other equally important finding we have made in our laboratory is the development of a simple and sensitive technique of quantitation of microembolism in brain, kidneys, lungs, and other visceral organs after implantation of cardiovascular prosthesis. This microembolism might cause neurological symptoms, tissue hypoxia, hypertension, and necrosis. This technique will enable us to study the turnover of microembolism and the role of platelet antiaggregating agents on patients implanted with a variety of cardiovascular prosthetic devices.